Anatomical, electrophysiological and pharmacological data on gustatory and visceral pathways suggest several testable hypotheses about the functional organization of the nucleus of the solitary tract (NST). The PI's laboratory has shown that taste cells in the NST are driven by peripheral taste fibers via excitatory amino acids, that these cells are tonically inhibited by GABA and that taste-responsive cells in the NST are excited and sometimes inhibited by the neuropeptide, substance P. The current application will extend these findings by addressing three specific aims. First, the mechanisms of inhibition in the NST and its role in shaping the responsiveness of gustatory neurons will be further investigated. Initial experiments will determine if GABAB and glycine receptors contribute to inhibition in the NST and if inhibition sharpens the breadth of tuning of NST neurons to gustatory stimuli. Additional experiments will determine if there are differences in inhibitory control between gustator neurons that relay information to the parabrachial nuclei (relay neurons) and those that do not (nonrelay neurons). The second aim is to determine the influence of descending inputs from the gustatory neocortex and the central nucleus of the amygdala on NST taste neurons. Initial experiments will examine the hypothesis that descending inputs from the neocortex and amygdala produce excitatory and inhibitory modulation of NST cells. Subsequent experiments will test the hypotheses that the excitatory inputs are mediated by excitatory amin acids and the inhibitory inputs by inhibitory amino acids. The final set of experiments in this aim will evaluate the hypothesis that relay neurons are modulated differently by central inputs than nonrelay neurons. The final specific aim will address the question of modulation of NST taste responses by neuropeptides, and in particular, the apparent preferential excitation of NaCl-best neurons by substance P. The effects of met-enkephalin on NST taste neurons and the possible differential modulation of neuropeptide effects on relay and nonrelay neurons will also be examined. These in vivo experiments ar designed to reveal how the synaptic interactions in the NST and the connection to and from this nucleus control responses of NST neurons to gustatory inputs. These studies will provide important new information for our understanding of the functional organization of the central gustatory system.